The Marine Natural Product, Halistanol Trisulfate, Inhibits pp60v-src Protein Tyrosine Kinase Activity

Halistanol trisulfate, a sulfated steroid derivative, was isolated from the extracts of two different marine sponges (genus Topsentia) by bioassay-guided fractionation. It exhibited an IC50 of approximately 4 mu M against pp60(v-src), the oncogenic protein tyrosine kinase encoded by Rous sarcoma virus. Removing the sulfate groups by acid hydrolysis produced the inactive tris-alcohol, halistanol. The kinetics of inhibition were examined and revealed that halistanol trisulfate Is a competitive inhibitor with respect to the peptide substrate, [val(5)]-angiotensin II, and a mixed inhibitor with respect to ATP. A number of monosulfated steroids were studied for protein tyrosine kinase inhibitory activity, but were found to be inactive. (C) 1994 Academic Press, Inc.